Patent EP 240228 describes a dibenzothiazepine compound of formula (I):
useful for its antidopaminergic activity, for example as an antipsychotic or neuroleptic, currently known by the DCI of quetiapine.
The said patent describes the obtaining of the compound of formula (I) by reaction of an imino chloride, specifically 11-chloro-dibenzo[b,f][1,4]thiazepine, or of its corresponding imino ether, with 2-(2-piperazine-1-il-ethoxy)ethanol.
A later patent, EP 282236, describes the preparation of the compound of formula (I) by reaction of the same imino chloride with piperazine, followed by reaction of the product obtained in hydrochlorate form with chloro-ethoxyethanol.
However, said procedures are carried out at high temperature (at xylene reflux (Teb=137-140° C.), and with mixtures of propanol and N-metthylpyrrolidone) over a long period of time, between 24 and 30 h, while also requiring a large excess of reagent in order to prevent undesired dialkylation reactions.
Later, international application WO 0155125 describes a procedure different from the preceding ones for obtaining the compound of formula (I). That procedure consists in reacting a derivative of haloethylpiperazineylthiazepine with ethylene glycol. This procedure requires both the use of sodium, an extremely strong deprotonisation agent, in order to generate the corresponding anion, and the use of a considerable excess of ethylene glycol (30 equivalents) in order to minimise the disubstitution reaction. The excess of ethylene glycol must be removed later with a large quantity of water, thereby generating a large quantity of residual aqueous products.
Furthermore, international application WO 9906381 describes a procedure for purifying the compound of formula (I), base quetiapine, by crystallisation and isolation as a solid. However, the implementation of this procedure has not permitted base quetiapine to be obtained in crystalline form.